It has long been known that cannabis can cause an acute psychotic episode and recent epidemiologic studies suggest that frequent cannabis use in adolescents can lead to an acute schizophreniform disorder that by itself develops into chronic schizophrenia. However, the majority of individuals who use cannabis do not develop a psychosis. Thus, some mechanism must underlie the development of psychosis in those that are affected. If cannabis is used in individuals with a genetic susceptibility for schizophrenia, it may interact with the genetic mechanism to initiate a psychosis that later develops into schizophrenia. Thus, the primary aim of this proposal will be to determine the effect of family history of schizophrenia in a first degree relative on subsequent development of schizophrenia in cannabis users. This issue will be examined by evaluating consecutive adolescent patients with a first psychotic episode subsequent to cannabis use and similar patients with an episode not subsequent to cannabis use that are admitted to two large NYC psychiatric emergency rooms. These individuals will have their family histories compared with adolescent cannabis users who never had a psychotic episode, and age, sex, and social class matched non-cannabis using controls. All available first-degree relatives with psychiatric symptoms will be interviewed to determine DSM-IV diagnoses, particularly of schizophrenia. All cannabis using subjects and non-cannabis using psychotic individuals will have a diagnostic follow-up evaluation for two years subsequent to the first episode to determine who among these subjects develops schizophrenia. The effect of genetic risk for schizophrenia on the development of schizophrenia in those with cannabis use will be explored. This study will aid in our scientific understanding of the relationship of cannabis to schizophrenia and ultimately have implications for early treatment strategies in adolescent cannabis users who are at high genetic risk for the disorder. [unreadable] Project Narrative: Cannabis abuse is a major public health problem, particularly in young adults. Recently there has been public interest in the connection between cannabis use and later development of the chronic disabling psychiatric disorder, schizophrenia. Some researchers believe that cannabis can damage the brain in some way to cause schizophrenia, while others do not. This proposed project will evaluate people who frequently use cannabis to determine whether only people who have a genetic vulnerability for schizophrenia will have this adverse effect of cannabis. If we are correct that genes for schizophrenia are needed for cannabis to lead to schizophrenia, one implication of this study will be that cannabis alone does not directly cause schizophrenia, but it may have an adverse effect on people who have inherited schizophrenia by interacting with the vulnerability genes in some way. Another implication of this study would be that people who have a family history of schizophrenia should be strongly cautioned from using cannabis and if they do as adolescents, be observed closely for adverse psychotic symptoms. [unreadable] [unreadable] [unreadable] [unreadable]